Expression of estrogen receptor beta in the breast carcinoma of BRCA1 mutation carriers

Background: Breast cancers (BC) in women carrying mutations in BRCA1 gene are more frequently estrogen receptor negative than the nonhereditary BC. Nevertheless, tamoxifen has been found to have a protective effect in preventing contralateral tumors in BRCA1 mutation carriers. The identification of the second human estrogen receptor, ER beta, raised a question of its role in hereditary breast cancer. The aim of this study was to assess the frequency of ER alpha, ER beta, PgR (progesterone receptor) and HER-2 expression in breast cancer patients with mutated BRCA1 gene and in the control group. Methods: The study group consisted of 48 women with BRCA1 gene mutations confirmed by multiplex PCR assay. The patients were tested for three most common mutations of BRCA1 affecting the Polish population (5382insC, C61G, 4153delA). Immunostaining for ER alpha, ER beta and PgR (progesterone receptor) was performed using monoclonal antibodies against ER alpha, PgR (DakoCytomation), and polyclonal antibody against ER beta (Chemicon). The EnVision detection system was applied. The study population comprised a control group of 120 BC operated successively during the years 1998-99. Results: The results of our investigation showed that BRCA1 mutation carriers were more likely to have ER alpha-negative breast cancer than those in the control group. Only 14.5% of BRCA1-related cancers were ER alpha-positive compared with 57.5% in the control group (P < 0.0001). On the contrary, the expression of ER beta protein was observed in 42% of BRCA1-related tumors and in 55% of the control group. An interesting finding was that most hereditary cancers (75% of the whole group) were triple-negative: ER alpha(-)/ PgR(-)/ HER-2(-) but almost half of this group (44.4%) showed the expression of ER beta. Conclusion: In the case of BRCA1-associated tumors the expression of ER beta was significantly higher than the expression of ER alpha. This may explain the effectiveness of tamoxifen in preventing contralateral breast cancer development in BRCA1 mutation carriers.